Abstract Project: Administrative Supplements to project - Tools and Methods for Producing High Quality Functional Protein Microarrays for Biomarker Discovery INanoBio is developing ProCap system capable of semi-automated production of functional protein arrays, which can be phosphorylated, de-phosphorylated by kinases, phosphatases in high throughput format, in addition to other PTM modifications. As described in our original SBIR project research plan, the ultimate goal is to use ProCap system to produce NAPPA IPC protein arrays on biosensor arrays, for real time detection of protein - protein, protein - enzyme interactions in high-throughput format. INanoBio aims to expand ProCap system to integrate protein microarrays with biosensors, that will boost ADRD research on identifying disease signaling pathways, discovering biomarkers for diagnostics and importantly for drug discovery screening. We have developed an advanced field effect transistor (FET) nano-sensor technology that can electronically detect Tau protein phosphorylation and de-phosphorylation with ultra-high sensitivity in real time, yielding kinetic readouts. Tau protein interaction with kinases and phosphatases plays a critical role in its hyper-phosphorylation that results in aggregation and formation of neruo toxic neurofibrillary tangles, a hallmark of Alzheimer's disease. Using supplemental funding, the project scope will be expanded to test methods for using ProCap system to produce and immobilize protein arrays comprising Tau kinases, phosphatases, followed by detecting Tau phosphorylation, de-phosphorylation using FET nano-sensor devices.